Ritonavir administered alone or in combination with reverse transcriptase inhibitors, demonstrated considerable antiretroviral activity in and were generally well tolerated by individuals with HIV-1 infection. This multiple-dose, open-label, randomized, multicenter trial in HIV-1-infected male and female patients with CD4 cell counts of 100-500 cells per microliter is assessing the efficacy and safety of the combination of ritonavir with saquinavir, a second protease inhibitor whose bioavailability is dramatically increased by co-administration with ritonavir. In addition, the study will determine whether this combination of protease inhibitors can retard or prevent the emergence of drug-resistant viruses. During the first year of study patients were randomized to one of the following four treatment regimens: ritonavir 400 mg BID and saquinavir 400 mg BID; ritonavir 600 mg BID and saquinavir 400 mg BID; ritonavir 400 mg TID and saquinavir 400 mg TID; and ritonavir 600 mg BID and saquinavir 600 mg BID. Subjects not achieving plasma RNA levels below 200 copies/ml were allowed to add up to 2 nucleoside inhibitors of reverse transcriptase to their regimen. Seventeen subjects were enrolled at this site, and 9 remain in the trial. The nine subjects who are still participating in the study have experienced a significant reduction in their viral activity. These nine subjects will be studied for an additional 52 weeks to further assess virologic response with serial viral RNA determinations using the Roche PCR assay.